欧前胡素对Aβ1-42致阿尔茨海默病小鼠学习记忆障碍的影响

摘要

研究欧前胡素(imperatorin,Imp)对Aβ1-42致阿尔茨海默病(Alzheimer's disease,AD)小鼠学习记忆的影响及机制.小鼠脑室内注射Aβ1-42制备AD模型,Imp 2.5 mg/kg和5.0 mg/kg在手术后当天开始腹腔注射给药,1次/d,连续给药13 d,正常对照组和模型组在相同的给药时间点给予溶媒0.1 mL/10 g.第14 d,采用跳台法观察小鼠的学习记忆功能,检测小鼠脑组织内活性氧簇(reactive oxygen species,ROS)、脂质过氧化产物丙二醛(malondialdehyde,MDA)和总抗氧化能力(Total antioxidant capacity,T-AOC)及ATP酶活性.研究显示,同AD模型组比较,Imp 2.5 mg/kg和5.0 mg/kg组小鼠的跳台潜伏期明显延长(P＜0.05,P＜0.01)和错误次数明显减少(P＜0.05,P＜0.01),Imp 2.5 mg/kg和5.0 mg/kg组小鼠脑组织中ROS和MDA含量明显降低(P ＜0.05,P＜0.01),Imp 5.0 mg/kg组T-AOC明显增强(P＜0.01),Imp 2.5 mg/kg和5.0 mg/kg组Na+、K+-ATP与Ca2+-ATP酶的活性明显增强(P＜0.05,P＜0.01).研究结果提示,Imp可能通过抑制AD小鼠脑组织中氧化应激损伤,从而改善Aβ1-42致AD小鼠的学习记忆功能.%To investigate the effects and mechanisms of imperatorin on learning and memory of beta-amyloid peptide1-42 (Aβ1-42)-induced model of Alzheimer's disease (AD) in mice.Mice were injected with Aβ1-42 intracerebroventricularly to induce AD model.Imperatorin (2.5,5mg/kg) were administered intraperitoneally once daily for 13 days,the normal control group and the AD model group were given the vehicle (0.1 mL/10 g) according to the same protocol.The learning and memory ability was evaluated by the step-down test,the contents of reactive oxygen species (ROS) and lipid peroxidation products malondialdehyde (MDA),the total antioxidant capacity (T-AOC) and the activity of Na+,K+ -ATPase and Ca2+-ATPase in the brain tissue were assayed.The results showed that as compared to the model group,administration of imperatorin significantly increased the latency and decreased the number of errors within 5 min in the step-down test.Furthermore,imperatorin treatment also significantly decreased the level of ROS and MDA,and enhanced T-AOC and the activity of Na+,K+-ATPase and Ca2+-ATPase in the brain tissue.These results suggested that imperatorin can significantly ameliorate the learning and memory impairment and the mechanism may be partly related to inhibiting oxidative stress in Aβ1-42-induced model of dementia in mice.